Familiar Food-Induced Feeding Activation in C. Elegans
The growing epidemic of obesity and eating disorders demands the study of regulatory mechanisms of food intake. Studying mutants whose food intake is altered under various conditions has greatly advanced our understanding of the mechanism. However, it is still largely unknown by which mechanisms perception of food activates food intake. The simple anatomy, genetic tractability, and well-characterized and quantifiable feeding behavior and evolutionary conservation of feeding regulators make C. elegans an attractive model system for the study. Food intake in C. elegans requires two muscle motions, pharyngeal pumping and isthmus peristalsis, and the frequencies of the two feeding motions dramatically increase in response to food as in other organisms. I attempted to understand the mechanism underlying food-induced feeding activation by studying the mechanism and the physiological context of action of serotonin, an endogenous activator of pharyngeal pumping. Here I show that like food, serotonin increases overall feeding by activating both feeding motions. Serotonin activates the two feeding motions by activating two distinct neural pathways. A 5-HT7 receptor activated the two motions mainly by acting in the two distinct pharyngeal motor neurons that are essential for food-induced feeding activation. Moreover, the results support that the serotonin receptor activated the two distinct neurons mainly by activating two distinct downstream G protein signaling pathways. Despite the separate regulation, isthmus peristalsis was coupled to the preceding pharyngeal pump. The separate regulation with coupling of the two feeding motions may have evolved to support efficient feeding by allowing control of the ratio of the frequencies of the two muscle motions according to density of food and by preventing futile isthmus peristalsis. Then, which aspect of food triggers the serotonin signal that increases food intake? I found that recognition of familiar food selectively triggers the serotonin signal. Worms selectively consume particular bacteria more actively after experience and the behavioral plasticity requires serotonin signaling. By dissecting the mechanism, I found that recognition of familiar food triggers serotonin release from a pair of chemosensory neurons. The released serotonin acts as an endocrine signal to increase pharyngeal pumping rate by activating the pharyngeal motor neuron that directly triggers pharyngeal pumping. The results suggest that worms form a memory of previously experienced food and that the memory controls food intake. Consistently, the familiar-food induced feeding was strongly dependent on duration of exposure to food to learn but not developmental timing of exposure or nutritional status. Furthermore, worms could remember the previously experienced food at least for several hours. My study provides insight into how feeding organ operates to increase food intake in response to food and how a particular aspect of food controls the process to increase food intake in C. elegans. Studying familiar food-induced feeding activation may help us understand the mechanisms underlying perception of different food and encoding, retention and retrieval of the memory of familiar food.